Effect of treatment of high fat fed/low dose streptozotocin-diabetic rats with Ilepatril on vascular and neural complications
Effect of treatment of high fat fed/low dose streptozotocin-diabetic rats with Ilepatril on vascular and neural complications
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DOI：
10.1016/j.ejphar.2011.07.016
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发表时间：
2011-10-15
影响因子：
5
通讯作者：
Yorek, Mark A.
中科院分区：
文献类型：
--
作者：
Davidson, Eric P.;Coppey, Lawrence J.;Yorek, Mark A.
我们之前已经证明，用 Ilepatril（中性内肽酶和血管紧张素转换酶 (ACE) 抑制剂）治疗链脲佐菌素诱导的糖尿病大鼠（一种 1 型糖尿病动物模型）可改善血管和神经功能。在这项研究中，我们试图确定 Ilepatril 治疗高脂肪喂养/低剂量链脲佐菌素糖尿病大鼠（2 型糖尿病模型）对血管和神经并发症的影响。高脂肪饮食 8 周后，大鼠接受 30 mg/kg 链脲佐菌素（腹腔注射）治疗，另外 4 周后，一组大鼠接受 Ilepatril 治疗 12 周，然后分析神经和血管功能。这些研究包括年龄匹配的对照大鼠和喂食高脂肪饮食并用或不用 llepatril 治疗的大鼠。糖尿病和饮食诱导的肥胖大鼠具有胰岛素抵抗、神经传导速度减慢、热痛觉减退、后爪表皮内神经纤维密度降低、坐骨神经外膜小动脉乙酰胆碱和降钙素基因相关肽血管舒张受损等特征。尽管对糖尿病大鼠胰岛素抵抗的改善甚微，但艾来帕曲治疗可有效改善所有这些终点。这些研究表明，双重抑制2型糖尿病大鼠的血管紧张素转换酶和中性内肽酶活性是治疗糖尿病神经和血管并发症的有效方法。由 Elsevier B.V. 出版
We have previously shown that treating streptozotocin-induced diabetic rats, an animal model of type 1 diabetes, with Ilepatril (an inhibitor of neutral endopeptidase and angiotensin converting enzyme (ACE)) improves vascular and neural functions. In this study we sought to determine the effect of Ilepatril treatment of high fat fed/low dose streptozotocin-diabetic rats, a model for type 2 diabetes, on vascular and neural complications. Following 8 weeks on a high fat diet rats were treated with 30 mg/kg streptozotocin (i.p.) and after 4 additional weeks a group of these rats was treated for 12 weeks with Ilepatril followed by analysis of neural and vascular functions. Included in these studies were age-matched control rats and rats fed a high fat diet and treated with or without llepatril. Diabetic and diet induced obese rats have characteristics of insulin resistance, slowing of nerve conduction velocity, thermal hypoalgesia, reduction in intraepidermal nerve fiber density in the hindpaw and impairment in vascular relaxation to acetylcholine and calcitonin gene-related peptide in epineurial arterioles of the sciatic nerve. Treatment with Ilepatril was efficacious in improving all of these endpoints although improvement of insulin resistance in diabetic rats was minimal. These studies suggest that dual inhibition of angiotensin converting enzyme and neutral endopeptidase activity of type 2 diabetic rats is an effective approach for treatment of diabetic neural and vascular complications. Published by Elsevier B.V.